Skip to main content
Search
Loading

Top investigators share research findings on biological signaling mechanisms that ensure robustness and wound repair.

September 13, 2024

This summer, over 50 researchers in the NSF EMBRIO Institute convened to share their newest findings on cellular signaling and organization that drives wound repair, cellular defense, and organismal robustness.  The EMBRIO Institute stands for Emerging Mechanisms in Biology of Robustness, Integration, and Organization, is one of 15 National Science Foundation Biology Integration Institutes. Investigators in the institute use imaging, computing, and AI in several biological organisms including plant and animal systems to address core rules of life questions.   The institute includes diverse investigators studying a core biological question across several species in the plant and animal kingdoms is led by Purdue University and includes 5 additional university partners.

During the meeting, hosted at Purdue University, a new competition was held to recognize the best work around producing scientific images, live cell videos, and simulations that convey the most impact and innovation, together with the degree of explaining the biological data, mechanisms, or processes.

Ongoing research pursues questions of how living systems integrate chemical and mechanical stimuli to develop robust cells and tissues, even when those tissues are injured. Answering these challenging questions may have potentially far-reaching impacts on our understanding of organismal health across plant and animal kingdoms- the cross species sharing and integration of knowledge is an example in practice of the ONE Health initiatives at Purdue. The National Science Foundation recognized the scientific merits of this Big Idea and awarded the Institute a five-year grant in late 2021 from the Biology Integration Institutes program, launched to support unique interdisciplinary and integrative science necessary to investigate complex questions in biology.

First Place Image or Video in the Graduate Division from Bakary Samasa: “Confocal microscopy reveals actin details in enveloping layer and yolk cell during epiboly morphogenesis in zebrafish.” Collaborators: Samasa B., Zinski J., Mullins M.C.
First Place Image or Video in the Graduate Division from Bakary Samasa: “Confocal microscopy reveals actin details in enveloping layer and yolk cell during epiboly morphogenesis in zebrafish.” (Collaborators: Zinski J., Mullins M.C.)


The first-place scientific images included a submission from Bakary Samasa (University of Pennsylvania) in the Graduate Division, and in the Postdoctoral and Research Scientist Division member voting resulted in a tie between Sharon Minsuk (Indiana University, Bloomington), and Weiwei Zhang (Purdue University). Bakary’s winning entry follows up on his earlier imaging success, a scientific image that became a U.S. Postage stamp! A high level of knowledge, skill, and innovative research was involved in producing the top images, live cell videos, and modeling simulation. Readers can view the winning submissions with background information and context at the EMBRIO website.

Samasa, a doctoral candidate mentored by Professor Mary Mullins in the Perelman School of Medicine at UPenn, is conducting research to elucidate the mechanisms of epiboly. Epiboly is one of several types of cell movement during early development of animal embryos that drive the embryo’s transformation into a fully formed individual. The Mullins lab studies zebrafish to investigate epiboly. Samasa explained,

“My research focuses on how the cytoskeleton and calcium interplay to drive the process of epiboly. I’ve been learning and employing various imaging modalities as well as mutant zebrafish in my efforts to determine the mechanisms of the morphogenetic process.”

As part of the collaborative framework of EMBRIO, each graduate student has at least one co-mentor from another department or university. Professor and Institute Executive Director and PI David Umulis, serves on Bakary’s doctoral committee. In addition to the Umulis Quantitative and Systems Biology Lab at Purdue, Samasa and Mullins are actively collaborating with Sharon Minsuk in the James Glazier lab at Indiana University to develop an accurate simulation of epiboly.

Samasa and Minsuk at Poster
Bakary Samasa (left), Ph.D. Candidate at UPenn and Dr. Sharon Minsuk (right), Research Fellow at IU, in front of Mr. Samasa’s research poster in July at the EMBRIO Annual Retreat. The two scientists collaborate as members of a larger team in the EMBRIO Institute. Photo: Brent T. Ladd, Purdue University

 

Minsuk, Research Fellow in the Biocomplexity Institute at Indiana University, submitted a video of Zebrafish epiboly simulation that tied for top place in the Postdoctoral and Research Scientist Division. Minsuk, along with Professor James Glazier, and former postdoc T.J. Sego (now at University of Florida), have been incorporating the knowledge gained from experimental biology performed by Samasa and Mullins at UPenn, and Linlin Li and David Umulis in Biomedical Engineering at Purdue. The recent iteration of the simulation has been able to more closely mirror the kinds of mechanical forces occurring in live embryos. Minsuk explains,

Embryos of all multicellular species go through a spectacular transformation from that first cell to the complex organisms they become. I’m especially interested in morphogenesis — the dramatic changes in shape of embryonic tissues that give rise to all these forms. My work is to simulate these processes in a computer, which not only tests our current understanding, but can stretch our ability to make predictions and can suggest new experiments.”

epiboly-simulation-stillpic.png
View the simulation of epiboly

Title: Zebrafish epiboly simulation with “laser cut” experiment by Sharon Minsuk (Collaborators: James Glazier, T.J. Sego, Mary Mullins, David Umulis). First Place (tie) in the Postdoctoral and Research Scientist Division
Center-based model of EVL (epithelial) expansion in response to forces generated outside the EVL. (In live embryos these forces are generated in the yolk cell cortex (red), which is mechanically coupled to the EVL leading edge cells (yellow) through tight junctions.) Individual cell-cell adhesive interactions are modeled as springs, hence are elastic;  but neighbor exchange leads to cell rearrangement (passive, in response to mechanical forces) which imparts viscoelasticity to the overall tissue as in live embryos, allowing permanent deformation. To demonstrate this, we disable the external force (timestamp 0:24), releasing the EVL from its mechanical coupling to the yolk, as in a laser cut experiment. We simultaneously disable the cell rearrangement, which is slow, so that the experiment reflects the instantaneous recoil behavior of the tissue, exhibiting a limited local recoil and then stabilizing. 


Moving from the Animal Kingdom with Zebrafish (Danio rerio) into the Plant Kingdom with Rockcress (Arabidopsis thaliana), Weiwei Zhang, Senior Plant Cell Biologist working in Chris Staiger’s  lab in Botany and Plant Pathology at Purdue, tied for first place with Minsuk in the Postdoc and Research Scientist Division.

Zhang-poster.jpg
Dr. Weiwei Zhang (right), Sr. Plant Cell Biologist, Purdue, presents collaborative EMBRIO research during the National Science Foundation’s Biology Integration Institutes Conference, January 2024. photo: Brent T. Ladd, Purdue University

 

I study how immunity works in plants so that they are resistant to various fungal and bacterial pathogens. I am investigating how plants detect the presence of potential pathogens, and how this recognition triggers a complex network of signaling pathways inside the plant cell.”, said Zhang. “I’ve been using state-of-the-art live-cell imaging tools combined with genetic and pharmacological perturbations to better understand plant tissue defense.”

Zhang’s and Staiger’s research have led to active collaborations across the Institute, including with labs at Purdue (Anjali Iyer-Pascuzzi's  lab, Elsje Pienaar's  lab, and Taeyoon Kim's  lab), Jeremiah Zartman’s Multicellular Systems Engineering lab  at University of Notre Dame, and Mauricio Cabrera-Rios and Clara Isaza with The Applied Optimization Group at University of Puerto Rico at Mayagüez.

CaWave-stillpic.png
View the live cell video of calcium waves propagating

Title: Intercellular Ca2+ waves propagate at a constant speed with limited travel distance during plant pattern-triggered immunity by Weiwei Zhang (collaborators: Chris Staiger, Elsje Pienaar, Anjali Iyer-Pascuzzi, Jeremiah Zartman). First Place (tie) in the Postdoctoral and Research Scientist Division An intercellular Ca2+ wave induced by the bacterial immunogenic peptide (see flg22 below) in Arabidopsis cotyledon epidermal cells expressing the Ca2+ reporter R-GECO1. Bar = 50 µm. Video playback rate = 20 frames per second. Total elapsed time = 245 s.  

 

Intracellular waves propagate in plant defense.png

Intercellular Ca2+ waves propagate at a constant speed with limited travel distance during plant pattern-triggered immunity.

(A, B) Two representative time series show the propagation of Ca2+ waves in Arabidopsis cotyledon epidermal cells treated with the bacterial immunogenic peptide flg22. Initiator cells of the waves are marked with an asterisk. Bars = 50 µm. (C–E) A pipeline for analysis of wave travel speed. A series of concentric circles was generated from the center of a wave (C). The mean fluorescence intensity for each circle ROI across the entire time series was extracted and a representative plot of the intensity profiles for all ROIs is shown in (D). The peak of each trace in (D) was identified and its corresponding value on the x-axis represents the time a wave travels to a given distance (radius of the circle). (E) The distances and peak times obtained in (D) were plotted and a linear curve was fitted to obtain the wave speed. (F) Kymographs generated from the yellow lines drawn in (A) and (B). A straight line could be fitted to the trajectory of the wave front (white dashed line), suggesting a constant speed. (G) Quantitative analysis of Ca2+ wave speed in seedlings treated with 0.01, 0.1, or 1 µM flg22. (H) Quantification of the density of Ca2+ wave initiation sites in cotyledon epidermis. (Data from 8–9 cotyledons from 3 biological repeats are presented; One-way ANOVA and Turkey’s HSD test, different letters indicate significant differences with P < 0.05.)

 

Interdisciplinary collaborations and team science, coupled with advances in both cell imaging technology and computational modeling of biological systems, are moving EMBRIO Institute scientists closer to a big picture understanding of how cells integrate and organize information to support robust development of tissues in the face of environmental and pathological challenges.

When asked about how collaborations in EMBRIO have benefited their own research goals, Minsuk had this to say,

"I believe a combined modeling and experimental approach can bring synergy and a deeper understanding than either approach can achieve on its own. As a former experimental embryologist and software developer moving into biophysical modeling, I couldn’t do what I’m doing without on the one hand, my experimentalist colleagues with their deep familiarity with the zebrafish embryo, and on the other hand my physicist colleagues with their theoretical insights about how to model and understand the deep underlying physical and mathematical structure of living tissue."

Asked the same question, Zhang responded,

As an experimental biologist with little prior experience in computational modeling, the EMBRIO projects have been a transformative opportunity. Collaborating closely with computational biologists to develop models and simulations of signaling processes in plant immunity has completely changed how I view biological processesnow through a mathematical lens. This collaboration has not only deepened our understanding of the intricate dynamics of cellular signaling but also inspired new hypotheses and experiments to push our research forward.

David Umulis, Executive Director of EMBRIO Institute, professor and researcher at Purdue, and Sr. Vice Provost of the Purdue in Indianapolis campus, has focused much of his research career on quantitative methods to understanding biological processes. Reflecting on the level of integrated interdisciplinary science necessary to make progress on Rules of Life questions, Umulis underscores the significant value that the Institute is adding to scientists’ experience,

“We’ve been able to achieve progress on the scientific questions in such a short time frame through the utilization of integrative tools such as computer simulation, AI, and shared reagents.  We also benefit from the foundation of the institute that established an inclusive, open, and collaborative framework focused on shared goals, an ambitious research target, and a new way of thinking to pursue research and academic excellence.  Our faculty and trainees are engaged in co-mentoring and learning through team science across disciplines to the benefit of our early career scientists like Mr. Samasa, Dr. Minsuk, and Dr. Zhang.”

 

To learn more about EMBRIO’s research and education efforts, visit the Institute’s website or Google Scholar page.

News Media Contact: email to laddb [at] purdue.edu

Writers: Brent T. Ladd, David M. Umulis